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CAS No. : | 2094-72-6 | MDL No. : | MFCD00074724 |
Formula : | C11H15ClO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MIBQYWIOHFTKHD-UHFFFAOYSA-N |
M.W : | 198.69 | Pubchem ID : | 98915 |
Synonyms : |
|
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | 3261 |
Hazard Statements: | H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonia In water at 20℃; for 2 h; | To a stirred mixture of 1-adamantanecarboxylic acid (11, 36.05 g, 200 mmol) and DMF (5 drops)in CH2Cl2 (360 mL) cooled in an ice-water bath was added thionyl chloride (26.17 g, 220 mmol) inone portion. The resulting mixture was refluxed until the evolution of HCl gas ceased (typicallywithin 2 h). The solvent and excess thionyl chloride were then removed on a rotary evaporator, andthe crude acid chloride 12 was dissolved in THF (100 mL). The resulting solution was then slowlyadded dropwise to stirred concentrated aqueous ammonia (400 mL) cooled in an ice-water bath.After addition, the resulting white slurry was stirred at room temperature for another 2 h, and thewhite precipitates were collected via vacuum filtration, washed with cold n-hexane and dried invacuo to afford 1-adamantanecarboxamide (13). White solid; 34.06 g (95percent); m.p. 177–179 °C(literature value, 185.5–191.7 °C [48]). 1H-NMR (DMSO-d6, 400 MHz) δ: 6.89 (brs, 1H), 6.62 (brs, 1H),1.93 (s, 3H), 1.73–1.74 (m, 6H), 1.60–1.68 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonia; In water; at 20℃; for 2h; | To a stirred mixture of 1-adamantanecarboxylic acid (11, 36.05 g, 200 mmol) and DMF (5 drops)in CH2Cl2 (360 mL) cooled in an ice-water bath was added thionyl chloride (26.17 g, 220 mmol) inone portion. The resulting mixture was refluxed until the evolution of HCl gas ceased (typicallywithin 2 h). The solvent and excess thionyl chloride were then removed on a rotary evaporator, andthe crude acid chloride 12 was dissolved in THF (100 mL). The resulting solution was then slowlyadded dropwise to stirred concentrated aqueous ammonia (400 mL) cooled in an ice-water bath.After addition, the resulting white slurry was stirred at room temperature for another 2 h, and thewhite precipitates were collected via vacuum filtration, washed with cold n-hexane and dried invacuo to afford 1-adamantanecarboxamide (13). White solid; 34.06 g (95%); m.p. 177-179 C(literature value, 185.5-191.7 C [48]). 1H-NMR (DMSO-d6, 400 MHz) delta: 6.89 (brs, 1H), 6.62 (brs, 1H),1.93 (s, 3H), 1.73-1.74 (m, 6H), 1.60-1.68 (m, 6H). |
With ammonia; In tetrahydrofuran; water; at 20℃; for 1h; | 1-Adamantanecarboxylic acid (7.4 g, 41 mmol) was heated to reflux with thionyl chloride (15 mL) and DMF (2 drops) for 3 h. The excess thionyl chloride was distilled off under reduced pressure, and the residual traces were removed in vacuo for 15 min. The residue was dissolved in THF (20 mL) and added to aq. NH3 (100 mL, 30%) with ice cooling and stirring. After stirring for 1 h at room temperature, the precipitate was filtered off, H2O (ca. 1 L) added, followed by CH2Cl2 (ca. 200 mL) until the entire solid dissolved. The organic layer was collected, dried (Na2SO^) and evaporated in vacuo for 5 h to give 1-adamantanecarboxamide (5.15 g) as a colourless solid; 1H NMR (200 MHz, CDCl3) S 5.75 (br), 2.05 (3H, br s), 1.89-1.88 (6H, m), 1.80-1.63 (6H, m). | |
With ammonia; In tetrahydrofuran; water; at 0 - 20℃; for 2h;Alkaline aqueous solution; | Adamantane-1-carboxyliotac acid (10 g, 55 mmol) was heated at reflux with thionyl chloride (15 mL) and dimethylformamide (1 drop) for 2 h under an inert atmosphere <n="29"/>Excess thionyl chloride was distilled off under vacuum. The residue was dissolved in THF (30 mL) and added to a solution of concentrated aqueous ammonia (135 ml_) at 0 0C. The reaction was stirred for 2 h at rt. The mixture was cooled to 10 0C and filtered to give the crude product, which was washed with water and dried to afford admantane-1-carboxamide (6.6 g, 67%). 1H NMR (CDCI3, 400 MHZ): delta=1.71-2.04 (t, 15H), 5.66-5.75 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; | EXAMPLE 2 (+)-(R)-1-(4-Pyridyl)ethyl 1-adamantanecarboxylate The method followed that described in Example 1, but using (+)-(R)-1-(4-pyridyl)ethanol (369 mg, 3.0 mmol) in THF (12 ml), n-butyllithium (2.5 M, 1.2 ml, 3.0 mmol) in hexane, and 1-adamantanecarbonyl chloride (656 mg, 3.3 mmol) in THF (3 ml). Chromatography, on elution with petrol-ether-triethylamine 200:50:1, afforded the title compound (754 mg, 88%). [alpha]D +25.8 (c 1, CHCl3); IR numax 1730 cm-1; 1 H-NMR (CDCl3) delta1.50 (3H, d, J 6.6 Hz, CHCH3), 1.73 and 1.93 (12H, 2s, adamantyl CH2), 2.04 (3H, s, adamantyl CH), 5.80 (1H, q, J 6.6 Hz, OCH), 7.23 (2H, d, J 6.1 Hz, Py 3 and 5H), 8.58 (2H, d, J 6.1 Hz, Py 2 and 6H); MS m/z 285 (M+). By passing hydrogen chloride gas through a solution of the product in ether, the hydrochloride was obtained, m.p. 164-166 C. Anal. Calcd: C, 67.17; H, 7.52; N, 4.35. Found: C, 67.58; H, 7.51; N, 4.36%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;dmap; In tetrahydrofuran; at 80℃; for 48h; | A mixture of <strong>[61296-22-8]2-amino-5-bromothiazole monohydrobromide</strong> (3.00 g, 11 ,5 mmol), 1-adamanianecarbonyl chloride (2.74 g, 13 8 mmol), A- dimethylaminopyridine (LlO g, 0,90 mmol) and triethylamine (3.20 mL, 23.0 mmol) in 100 mL of THF was stirred at 80 0C for 48 hours The mixture was cooled to ambient temperature, diluted with 100 mL of ethyl acetate and washed with brine. <n="44"/>The layers were separated and the aqueous phase was extracted with 2 X 50 mL ethyl acetate The combined organic extracts were dried over anhydrous Na2SOd, filtered, and concentrated Purification by column chromatography (SiOi, 20% ethyl acetate: 80% hexane) afforded 2 55 g of the title compound 1H NMR {400 MHz, DMSO-(Z6) delta 1 67 - 1 72 (m, 6 H) 1 92 (d, ./=2 8 Hz, 6 H) 1 97 - 2 04 (m, 3 H) 7 55 (s, 1 H) 1 1 50 (br m, 1 H); MS (DCI/NH3) m/z 341 (M)+, 343 (M+2)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4,5-Dimeiotahyl~thiazol-2-ylamine and 2-(2-bromo-ethoxy)-l )l,l-trifiuoio- ethane were mixed and heated at 65 0C foi 4 hours The iesidue was triturated with hexane to affoid the title compound MS (ESI+) m/z 255 (M+eta)+; To a solution of Example 85 A (0 20 g, 0 8 mmol) in TetaF (10 mL) was added triethylamine (0 4 mL) and adamantane-1-caibonyl chloride (0 2 g, 1 mmol). The mixture was heated at ieflux overnight and then concentrated under reduced pressure The residue was diluted with ethyl acetate, washed with IM aqueous NaHCO3, dried (Na2SO1S), filtered, and concentrated Purification by preparative etaPLC on a Waters Symmetry C8 column (40 mm X 100 mm, 7 mum particle size) using a gradient of 10 % to 100 % acetonitrile: ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes afforded 10 mg of the title compound 1H NMR (300 MHz, DMSO- d6) delta ppm 1 60 - 1.75 (m, J=28 8 Hz, 6 H), 1.83 (d, J=2.7 Hz, 6 H), 1 93 - 2 01 (m, 3 H), 2 15 (s, 3 H), 2.20 (s, 3 H), 3 92 (t, J=5.3 Hz, 2 H), 4 09 (q, J-9.5 Hz, 2 H), 4,28 (t, >5.3 Hz, 2 H); MS (ESI+) m/z 417 (M+H)+; Anal Calculated for C20Hi7F3N2O2S: C, 57.67; H, 6 53; N, 6 73. Found: C, 57 53; H, 6 55; N, 6 69, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | To a solution of 4,5~dimethyl-ihiazo3-2-ylamine hydrochloride (1 65 g, 10 0 mmol) in TetaF (100 mL) was added tiiethylamine (4 2 mL, 30 mmol) and adamantane-l-carbonyl chloride (2 2 g, 1 1 mmol) The mixture was heated at reflux overnight and then concentrated under reduced pressure The residue was diluted with ethyl acetate, washed with IM NaHCO3, dried (Na2SO4), filtered and concentrated Purification by column chromatography (SiO2, 10 %ethyl acetate: 90% hexanes) afforded 2 15 g (74%) of the title compound MS (ESI+) m/z 291 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;dmap; In tetrahydrofuran; at 80℃; for 48h; | A mixture of 5-bromothiazol-2-amine (3 Og, 1 1 5 mmol), adamantane-1 - carbonyl chloride (2 74 g, 13 8 mmol), tiiethylamine (3 2 mL, 23 mmol) and 4- di(methylamino)pyridine (1.1 g) in tetrahydrofuran ( 100 mL) was heated at 80 0C for 48 hours The mixture was cooled to ambient temperature1, concentrated, diluted with water and extracted with ethyl acetate The organic extract was dried (Na2SO4), filtered and concentrated Purification by flash chromatography (silica gel, 25percent ethyl acetate /hexanes) afforded the title compound. MS (ESI) m/z 342 (M+H)"1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethylamine; | Due to the versatility with which adamantyl amide analogues can be synthesized by combining the commercially available 1-adamantylcarbonyl chloride with amino-acid methyl and ethyl esters, a series of adamantyl amnide analogues was synthesized. The resulting methyl and ethyl esters in all but one case were readily converted to the corresponding acids by saponification with lithium hydroxide as shown in (Scheme30). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With triethylamine; | Due to the versatility with which adamantyl amide analogues can be synthesized by combining the commercially available 1-adamantylcarbonyl chloride with amino-acid methyl and ethyl esters, a series of adamantyl amnide analogues was synthesized. The resulting methyl and ethyl esters in all but one case were readily converted to the corresponding acids by saponification with lithium hydroxide as shown in (Scheme30). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With sodium carbonate; In dichloromethane; water; at 20℃; for 2.0h; | Example 6: (5)-3-(l '-Adamantanecarbonyl)amino-caprolactam:(>S)-3-amino-caprolactam hydrochloride 2 (1 mmol) and Na2C03 (3 mmol) in water (15 ml) were added to a solution of 1-adamantanecarbonyl chloride (1 mmol) in dichloromethane (15 ml) at ambient temperature and the reaction was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 ml). The combined organic layers were dried over Na2C03 and reduced in vacuo. The residue was recrystallised from CH2C12 / hexanes to give (S)-3-(l '-adamantanecarbonyl)amino-caprolactam (171 mg, 59%); m.p. 256-258 C; [a]f (c = 1, CHC13) +29.5; vjcm'1 3411, 3259 (NH), 1678, 1626 (CO), 1505 (NH); 5H (500 MHz, CDC13) 7.08 (1H, d, J5.5, CHNH), 6.67 (1H, br s, CH2NNo.), 4.47 (1H, ddd, J11, 5.5, 1.5, CHNH), 3.32-3.17 (2H, m, CNo.2NH), 2.06-1.94 (5H, m, 2 x ring CH + 3 x adamantane CH), 1.90-1.75 (8H, m, 2 x ring CH + 3 x adamantane CH2), 1.72 (3H, br d, J 14.5, 3 x adamantane CHH), 1.68 (3H, br d, J 14.5, 3 x adamantane CHH) and 1.47-1.32 (2H, m, 2 x ring CH); 5C (125 MHz, CDC13) 177.2, 175.9 (CO), 51.9 (NHCHCO), 42.2 (CH2N), 40.5 (CCO), 39.0 (3 x CH2 adamantane), 36.5 (3 x CH2 adamantane), 31.7, 28.9, 28.0 (CH2 lactam), 28.1 (3 x CH adamantane); m/z (MH4 C17H27N202 requires 291.2073) 291.1994. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine; In tetrahydrofuran; at 20℃; for 2h; | Example 1 A^-(2-methylphenyl)adamantane- 1 -carbohydrazide; To an oven-dried, 25-mL, round-bottomed flask containing a magnetic stir bar was added the hydrochloride salt of o-tolylhydrazine (174 mg, 1.10 mmol). The flask was sealed with a septum and purged with nitrogen atmosphere. Anhydrous tetrahydrofuran (9 niL) was added via syringe to form a white slurry. Triethylamine (419 muL, 3.00 mmol) was added via syringe. A solution of 1-chlorocarbonyl adamantane (199 mg, 1.00 mmol) in anhydrous tetrahydrofuran (1 niL) was added. The white slurry was stirred at room temperature for 2 hours and then monitored by LC-MS (Hewlett-Packard 1100 HPLC with a Finnigan EPO <DP n="22"/>Navigator MS; C18 reverse phase column; 10-100% acetonitrile:10 mM ammonium acetate gradient; APCI positivie ionization) Water (10 mL) was added to quench and the reaction mixture was transferred to a separatory funnel. The mixture was extracted with dichloromethane (3 x 8 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give an off-white solid. The product was re-crystallized from ethyl acetate/hexanes to give 220 mg (77%) of a white powder. MS (ESI+) m/z 285.1 (M+H)+; 1HNMR (CDCl3) delta 1.72-1.81 (m, 6H), 1.95-1.96 (m, 6H), 2.09 (br s, 3H), 2.26 (s, 3H), 3.60 (br s, IH), 6.78-6.86 (m, 2H), 7.06-7.13 (m, 2H), 7.38 (br s, IH). Anal. Calc'd for C18H24N2O: C, 76.02; H, 8.51; N, 9.85. Found: C, 75.72; H, 8.73; N, 9.75. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | Adamantan-l-yI-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-methanone (STX1721, XDS04025);To a solution of 1-adamantanecarbonyl chloride (lOOmg, 0.50 mmol, 1.06 eq.) in DCM (5 mL) was added triethylamine (0.15 mL), followed by the 4,5,6,7-Tetrahydrothieno[3,2- c]pyridine (155mg, purity unknown). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-Trisamine (10-20 mg) was added. After stirred at ambient temperature for another 2h, the mixture was filtered and evaporation of the solvent gave a residue that was purified by flash chromatography (Hexane-Ethyl acetate/hexane gradient elution) to give crystalline solid (49 mg, 33 %). mp 141-143 0C; TLC single spot at Rf. 0.49 (20% ethyl acetate/hexane); 1H NMR (270 MHz3 CDCl3) delta 1.72 (6H, s, 3 x CH2), 2.02 (9H, s, 3 x CH and 3 x CH2), 2.88 (2H, t, J= 4.6 Hz5 CH2), 3.94 (2H, t, J= 4.5 Hz, CH2), 4.69 (2H, s, CH2), 6.79 (IH, d, J= 5.2 Hz, ArH) and 7.11 (IH, d, J= 5.2 Hz3 ArH); LC/MS (APCI) m/z 302 (M÷+H); HPLC tr = 3.24 min (>99 %) in 10% water-acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pyridine; water; ethyl acetate; | EXAMPLE 5 To a solution of 1-adamantanecarbonylchloride (39.73 g) in pyridine (260 ml) was added 4-carbamoylimidazolium-5-olate (12.71 g) and the reaction temperature was maintained at 41-43 C. for 3.5 hours. Pyridine was removed under reduced pressure. To the residue was added ethylacetate (300 ml) and water (300 ml), and stirred at room temperature for 1 hour. The insoluble solid was filtered and washed with ethyl acetate to give almost pure 5-carbamoyl-1H-imidazol-4-yl 1-adamantanecarboxylate (25.9 g, beta form, m.p. 205-205.5 C. (dec.)). Recrystallization from dimethylformamide-diethylether gave analytically pure sample (beta form m.p. 213.5-216.5 C. (dec.)). | |
With triethylamine; In N-methyl-acetamide; water; ethyl acetate; | EXAMPLE 6 To a suspension of 4-carbamoylimidazolium-5-olate (1.016 g) in dimethylformamide (20 ml) was added triethylamine (1.942 g) at 0-5 C. and then 1-adamantanecarbonylchloride (3.50 g) in dimethylformamide (20 ml) dropwisely over 24 minutes. The reaction mixture was stirred at 0-5 C. for 23 hours. The solvent was removed under reduced pressure. To the residue was added ethyl acetate (20 ml) and water (20 ml), and stirred at room temperature for 1 hour. The insoluble solid was filtered and washed with ethyl acetate to give almost pure 5-carbamoyl-1H-imidazol-4-yl 1-adamantanecarboxylate (1.5 g, alpha form, m.p. 206.5-207.5 C. (dec.)), which was washed thoroughly with ethyl acetate to give pure product, alpha form, m.p. 211 C. (dec.). | |
With triethylamine; In N-methyl-acetamide; water; ethyl acetate; | EXAMPLE 9 To a suspension of 4-carbamoylimidazolium-5-olate (4.064 g) in dimethylformamide (80 ml) was added triethylamine (7.768 g) at 0-5 C. and then 1-adamantanecarbonylchloride (14.00 g) in dimethylformamide (80 ml) dropwisely over 22 minutes. The reaction mixture was stirred at 0-5 C. for 15 hours. The solvent was removed under reduced pressure. To the residue was added ethyl acetate (100 ml) and water (100 ml), and stirred at room temperature for 1 hours. The insoluble solid was filtered and washed with ethyl acetate to give almost pure 5-carbamoyl-1H-imidazol-4-yl 1-adamantanecarboxylate (5.67 g, beta form, m.p. 207-210 C. (dec.)). |
In pyridine; water; ethyl acetate; | EXAMPLE 7 To a solution of 1-adamantanecarbonylchloride (2.980 g) in pyridine (26 ml) was added 4-carbamoylimidazolium-5-olate (1.271 g) and the reaction temperature was kept at 40-43 C. for 4 hours. Unreacted starting material was recovered by filtration (210 mg). The filtrate was concentrated under reduced pressure. To the residue was added ethyl acetate (30 ml) and water (30 ml), and stirred at room temperature for 1 hour. The insoluble solid was filtered and washed with ethyl acetate to give almost pure 5-carbamoyl-1H-imidazol-4-yl 1-adamantanecarboxylate (1.602 g, alpha form, m.p. 207-209 C. (dec.)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In diethyl ether; water; Petroleum ether; | EXAMPLE 31 3-(1-Adamantanecarbonyl)-8-Oxa-3-Azabicyclo(3.2.1)Octane SPC10 1-Adamantanecarbonyl chloride (19.87 grams, 0.1 mole, pulverized) (Aldrich Chemical Co., Inc., Milwaukee, Wisc.) was added to a mixture of 8-oxa-3-azabicyclo(3.2.1)octane hydrochloride (14.96 grams, 0.1 mole) and sodium hydroxide (10 grams) in 300 ml water. The reaction mixture was heated at 30 C. for 3 hours and then left overnight at room temperature. The product (22 grams) was filtered off, washed with water, and finally recrystallized from a blend of about 30% petroleum ether (boiling point 30-60 C.) and 70% diethyl ether (v/v). The product had a melting point of 134-136 C. Analysis for C17 H25 NO2. Calculated: C, 74.14%; H, 9.15%; N, 5.08%. Found: C, 74.10%; H, 9.21%; N, 5.06%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium carbonate; In dichloromethane; water; at 20℃; for 18h; | Example 1: - (S)-3-(l'-Adamantanecarbonylamino)-tetrahydropyridin-2-one:; ()S)-3-Amino-tetrahydropyridin-2-one hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (25 ml) were added to a solution of adamantane-1-carbonyl chloride (2 mmol) in dichloromethane (25 ml) at ambient temperature and the reaction was stirred for 18 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane. The combined organic layers were dried over Na2SO4 and reduced in vacuo. The residue was recrystallised from CH2Cl2 / hexanes to give the lactam as an amorphous solid (237 mg, 43%); vmjcm l 3330, 3175 (NH), 1655, 1683 (CO), 1500 (NH); deltaH (400 MHz, CDCl3) 6.59 (IH, br d, J4.5, NH), 6.51 (IH, br s, NH), 4.15 (IH, dt, J lO, 5.5, CHNH), 3.35-3.24 (2H, m, CH2NH), 2.57-2.48 (IH, m, lactam CH2), 1.99 (3H, br s, 3 x adamantane CH), 1.92-1.17 (8H, m, 2 x lactam CH and 6 x adamantane CH2), 1.73-1.61 (6H, m, 6 x adamantane CH2) and 1.45 (IH, tt, J 12.5, 8.5, lactam CH); deltac (100 MHz, CDCl3) 178.2, 172.2 (CO), 50.3 (NHCHCO), 41.5 (CH2N), 40.6 (CCO), 39.1 (3 x CH2 adamantane), 36.5 (3 x CH2 adamantane), 28.1 (3 x CH adamantane), 27.0, 21.0 (CH2 lactam); m/z (MNa+ C16H24N2O2Na requires 299.1735), 299.1739, (MH+ C16H25N2O2 requires 277.1916) 277.1919. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With triethylamine; In dichloromethane; at 0℃; for 3h; | A solution of 1 -admantanecarbonyl chloride ( 1 .6 g, 8 mmol) in dichloride (5 mL) was added dropwise to a solution of <strong>[39115-94-1]3-iodobenzohydrazide</strong>(2.0 g, 7.6 mmol) and triethylamine (1.0 g, 10 mmol) in dichloride ( 15 mL) at 0C with stirring. After stirring for an additional 3h at 0C, saturated ammonium chloride (30 mL) was poured into the mixture, and the organic layer was separated and washed subsequently with saturated sodium biscarbonate aqueous solution (30 mL), water (30 mL) and dried over anhydrous sodium sulfate. Upon removal of sodium sulfate by filtration and solvent under reduced pressure, the resulting residue was rinsed with ether to give a white solid 980 mg. Yield: 27%. (300MHz, CDC13): delta 10.4(s, 1 H), 8.6(s, 1 H), 8.35-8.34(m, 1 H), 8.04-8.00(m, 1 H), 7.85-7.81 (m, 1 H), 7.26-7.19(m, 1 H), 1.9 (s, 2H), 1.68-1.54(m, 13H). EI-MS (m/z): M+ calcd for C18H21 I 2O2, 424.28; found 425.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of the 1-adamantane carbonyl chloride (0.50 mmol, 1.06 equiv) in DCM (5 mL) was added triethylamine (0.15 mL), followed by the corresponding amine (0.47 mmol, 1 equiv). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-Trisamine (10-20 mg) was added. After stirring at ambient temperature for another 2 h, the mixture was filtered and evaporation of the solvent gave a residue that was purified by flash chromatography (ethyl acetate-DCM gradient elution) to give the desired carboxamide derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of the 1-adamantane carbonyl chloride (0.50 mmol, 1.06 equiv) in DCM (5 mL) was added triethylamine (0.15 mL), followed by the corresponding amine (0.47 mmol, 1 equiv). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-Trisamine (10-20 mg) was added. After stirring at ambient temperature for another 2 h, the mixture was filtered and evaporation of the solvent gave a residue that was purified by flash chromatography (ethyl acetate-DCM gradient elution) to give the desired carboxamide derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of the 1-adamantane carbonyl chloride (0.50 mmol, 1.06 equiv) in DCM (5 mL) was added triethylamine (0.15 mL), followed by the corresponding amine (0.47 mmol, 1 equiv). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-Trisamine (10-20 mg) was added. After stirring at ambient temperature for another 2 h, the mixture was filtered and evaporation of the solvent gave a residue that was purified by flash chromatography (ethyl acetate-DCM gradient elution) to give the desired carboxamide derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of the 1-adamantane carbonyl chloride (0.50 mmol, 1.06 equiv) in DCM (5 mL) was added triethylamine (0.15 mL), followed by the corresponding amine (0.47 mmol, 1 equiv). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-Trisamine (10-20 mg) was added. After stirring at ambient temperature for another 2 h, the mixture was filtered and evaporation of the solvent gave a residue that was purified by flash chromatography (ethyl acetate-DCM gradient elution) to give the desired carboxamide derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile; at 20℃; for 0.5h; | General procedure: To a solution of tetrahydro-2H-pyran-4-carbonyl chloride (100 mg, 0.7 mmol) in ACN (1.5 mL, 0.5 M) was added <strong>[42105-26-0]but-3-yn-2-amine hydrochloride</strong> (107 mg, 1.01 mmol) followed by triethylamine (142 muL, 1.01 mmol). The reaction mixture was stirred at room temperature for 30 min. AuCl3 (10 mg, 0.034 mmol) was added and the reaction mixture was stirred at 45 C for 2-3 h until complete conversion to the product which was detected by LCMS. After filtration and concentration, the crude oil was purified directly on SiO2 (12 g column eluted with 0-25% ethyl acetate-heptanes) to give a clear oil of 4,5-dimethyl-2-(tetrahydro-2H-pyran-4-yl)oxazole (83 mg, 68% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With pyridine;Inert atmosphere; Reflux; | The reaction was performed with 5-(2'-pyridyl)-1H-tetrazole (500 mg, 3.40 mmol) and 1-adamantanecarboxylic acid chloride (675 mg, 3.40 mmol, Acros) in pyridine (3.5 mL). The reaction mixture was extracted with ether/H2O. The organic layer was washed with water (to remove pyridine) and evaporated. Purification by column chromatography was performed on silica (10 g). Elution with CH2Cl2 removed the impurities. Elution with 0.5% of CH3OH in CH2Cl2 recovered the product. It was re-dissolved in ether, and hexane (20 mL) was added. The ether was rotor-evaporated to leave a suspension of the product in hexane. The suspension was cooled to -15 C overnight and filtered. The product was washed with cold hexane. The product purified in this way contained 10% of 1-adamantanecarboxylic acid (detected by 1H and 13C NMR). To remove the acid, the product was sonicated in saturated aqueous solution of Na2CO3 for 10 min and extracted with ether. The organic layer was washed with saturated aqueous solution of Na2CO3 and water. It was evaporated, and the extraction with Na2CO3 (aq. sat.) and ether was repeated one more time. White solid: 477 mg (1.70 mmol, 50%). Anal. Calc. for C17H19N3O (MW 281.35): C, 72.57; H, 6.81; N, 14.94. Found: C, 72.54; H, 6.87; N, 14.74%. 1H NMR (400 MHz, [D6]dmso): delta = 8.79-8.74 (m, 1H), 8.19-8.13 (m, 1H), 8.03 (td, J = 8.0, 1.6 Hz, 1H), 7.62 (ddd, J = 7.6, 4.8, 1.2 Hz, 1H), 2.10-2.04 (m, br, 9H), 1.77 (br, 6H) ppm. 13C NMR (100 MHz, CD2Cl2): delta = 173.68, 163.90, 150.34, 144.25, 137.28, 125.72, 123.00, 40.12, 36.44, 34.71, 28.13 ppm. GC-EI+ MS: m/z 281 (M+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | General procedure: A mixture of 24.5 mg (0.18 mmol) 1,2,3,4-tetrahydroquinoline, 37.3 mg (0.188 mmol) 1-adamatanecarbonyl chloride and 44.4 mg (0.34 mmol) DIPEA in 1 mL DCM was shaken at room temperature for 4 h. The mixture was evaporated, dissolved in DMF and subjected to column chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid to yield after evaporation of the product containing fractions 34.9 mg (64%) of the title compound as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With pyridine; In 1,4-dioxane; at 110℃; for 16h; | Example 3 l-(Adamantane-l-carbonyl)-2,3-dihydro-lH-quinolin-4-one A mixture of 25.2 mg (0.17 mmol) 2,3-dihydroquinolin-4(lH)-one and 52.9 mg (0.26 mmol) adamatanecarbonyl chloride in 0.9 mL dioxane and 0.041 mL pyridine was shaken at 110 C for 16 h. The mixture was evaporated, dissolved in DMF and subjected to column chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid to yield after evaporation of the product containing fractions 11.5 mg (22 %) of the title compound as white solid. MS(m/e): 310.4 (MH+). |
22% | With pyridine; In 1,4-dioxane; at 110℃; for 16h; | Example 3 1-(Adamantane-1-carbonyl)-<strong>[4295-36-7]2,3-dihydro-1H-quinolin-4-one</strong> A mixture of 25.2 mg (0.17 mmol) <strong>[4295-36-7]2,3-dihydroquinolin-4(1H)-one</strong> and 52.9 mg (0.26 mmol) adamatanecarbonyl chloride in 0.9 mL dioxane and 0.041 mL pyridine was shaken at 110 C. for 16 h. The mixture was evaporated, dissolved in DMF and subjected to column chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid to yield after evaporation of the product containing fractions 11.5 mg (22%) of the title compound as white solid. MS(m/e): 310.4 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In cyclohexane; at 10℃; for 6h; | General procedure: The N-acylation of racemic 1, 2, and 3 was carried out with acyl chlorides as acylation reagents and triethylamine as the base in cyclohexane in the presence and absence of TIPS-beta-CD. After a mixture of racemic 1, 2, and 3 (6.0x10-4 mmol) and 6-O-silylated beta-CD was stirred for 1 h in cyclohexane (600 muL) to reach the complexation equilibrium between 1, 2, and 3 and 6-O-silylated beta-CD, triethylamine (6.0x10-4 mmol), the acyl chlorides 4a-j were added at 10 C. The mixture was then stirred at 10 C for 6 h. The resulting products were analyzed by HPLC using the chiral phase column Diacel Chiralcel OD-H (250mm x4.6mm i.d.) using hexane/2-propanol=80:20 or 95:5 as an eluent at a flow rate of 0.5 or 1.5 mL min-1 using UV detection (254 nm). The HPLC charts of the products obtained after N-acylation of 1, 2, and 3 (6.0x10-4 mmol) with acyl chlorides 4a-j (3.3x10-4 mmol) in cyclohexane (600 muL)including triethylamine (6.0x10-4 mmol) in the absence and presence of TIPS-beta-CD (3.0x10-3 mmol) are shown in Figs. S18-26,respectively |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With heptakis (6-O-triisopropylsilyl)-beta-cyclodextrin; triethylamine; In cyclohexane; at 10℃; for 6h;Resolution of racemate; | General procedure: The N-acylation of racemic 1, 2, and 3 was carried out with acyl chlorides as acylation reagents and triethylamine as the base in cyclohexane in the presence and absence of TIPS-beta-CD. After a mixture of racemic 1, 2, and 3 (6.0x10-4 mmol) and 6-O-silylated beta-CD was stirred for 1 h in cyclohexane (600 muL) to reach the complexation equilibrium between 1, 2, and 3 and 6-O-silylated beta-CD, triethylamine (6.0x10-4 mmol), the acyl chlorides 4a-j were added at 10 C. The mixture was then stirred at 10 C for 6 h. The resulting products were analyzed by HPLC using the chiral phase column Diacel Chiralcel OD-H (250mm x4.6mm i.d.) using hexane/2-propanol=80:20 or 95:5 as an eluent at a flow rate of 0.5 or 1.5 mL min-1 using UV detection (254 nm). The HPLC charts of the products obtained after N-acylation of 1, 2, and 3 (6.0x10-4 mmol) with acyl chlorides 4a-j (3.3x10-4 mmol) in cyclohexane (600 muL)including triethylamine (6.0x10-4 mmol) in the absence and presence of TIPS-beta-CD (3.0x10-3 mmol) are shown in Figs. S18-26,respectively |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (2g, 10.1 mmol) and <strong>[2744-08-3]decahydroisoquinoline</strong> (3) (1.59ml, 1 1 .1 mmol) in DCM (20ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20muIota_ aliquot into MTBE:1 N HCI (400muIota_:400muIota_)] showed the formation of a single product. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a white solid. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (2g, 10.1 mmol) and <strong>[2744-08-3]decahydroisoquinoline</strong> (3) (1.59ml, 1 1 .1 mmol) in DCM (20ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20muIota_ aliquot into MTBE:1 N HCI (400muIota_:400muIota_)] showed the formation of a single product. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a white solid. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1.93 ml, 11.1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1-carbonyl chloride (1) (2 g, 10.1 mmol) and <strong>[2744-08-3]decahydroisoquinoline</strong> (3) (1.59 ml, 11.1 mmol) in DCM (20 ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20 muL aliquot into MTBE:1 N HCl (400 muL:400 muL)] showed the formation of a single product. The solution was washed with 0.1 N HCl (30 ml), saturated NaHCO3 (30 ml), dried (Na2SO4), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (1 g, 5.5mmol) and <strong>[38646-68-3]4,4-dimethylpiperidine hydrochloride</strong> (4) (828mg, 5.5mmol) in DCM (10ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20muIota_ aliquot into MTBE:1 N HCI (400muIota_:400muIota_)] showed the formation of a single chemical. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a crystalline white solid. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (1 g, 5.5mmol) and <strong>[38646-68-3]4,4-dimethylpiperidine hydrochloride</strong> (4) (828mg, 5.5mmol) in DCM (10ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20muIota_ aliquot into MTBE:1 N HCI (400muIota_:400muIota_)] showed the formation of a single chemical. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a crystalline white solid. | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1.93 ml, 11.1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1-carbonyl chloride (1) (1 g, 5.5 mmol) and <strong>[38646-68-3]4,4-dimethylpiperidine hydrochloride</strong> (4) (828 mg, 5.5 mmol) in DCM (10 ml) and the solution stirred at room temperature for 4 hours. At this time, TLC [15:85 EA:hexane, 20 muL aliquot into MTBE:1 N HCl (400 muL:400 muL)] showed the formation of a single chemical. The solution was washed with 0.1 N HCl (30 ml), saturated NaHCO3 (30 ml), dried (Na2SO4), filtered and the solvents removed to give crude product which was further purified by FC on silica gel using 15:85 EA:hexane to give the desired product as a crystalline white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (2g, 10.1 mmol) and <strong>[88675-24-5]3-aminotetrahydrofuran</strong>; (29)(1 .0ml, 1 1 mmol) in DCM (20ml) and the solution stirred at room temperature for 4 hours. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified via crystallization from 15percent EA in hexanes to give as a white solid | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1 .93ml, 1 1 .1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1 - carbonyl chloride (1 ) (2g, 10.1 mmol) and <strong>[88675-24-5]3-aminotetrahydrofuran</strong>; (29)(1 .0ml, 1 1 mmol) in DCM (20ml) and the solution stirred at room temperature for 4 hours. The solution was washed with 0.1 N HCI (30ml), saturated NaHC03 (30ml), dried (Na2S04), filtered and the solvents removed to give crude product which was further purified via crystallization from 15percent EA in hexanes to give as a white solid | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | DIPEA (1.93 ml, 11.1 mmol) was added to a solution of Tricyclo[3.3.1.13,7]decane-1-carbonyl chloride (1) (2 g, 10.1 mmol) and <strong>[88675-24-5]3-aminotetrahydrofuran</strong>; (29)(1.0 ml, 11 mmol) in DCM (20 ml) and the solution stirred at room temperature for 4 hours. The solution was washed with 0.1N HCl (30 ml), saturated NaHCO3 (30 ml), dried (Na2SO4), filtered and the solvents removed to give crude product which was further purified via crystallization from 15percent EA in hexanes to give as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 39 Adamantan-1-yl-(5,6-difluoro-2,3-dihydro-indol-1-yl)-methanone In analogy to the procedure described for the synthesis of adamantan-1-yl-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone (example 1) the title compound was prepared from <strong>[954255-04-0]5,6-difluoroindoline</strong> and adamatanecarbonyl chloride as light brown solid. MS(m/e): 318.3 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With dmap; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃;Inert atmosphere; | 1g of PEG monomethyl ester (PEG5000: 0.2mmol; PEG500: 2.1mmol) was dissolved in anhydrous DCM (PEG5000: 25ml; PEG500: 150ml) and cooled to 0C. Adamantane carbonyl chloride (5eq), DIPEA (10eq) and DMAP (1% cat.) were added and the mixture warmed to room temperature and stirred overnight under nitrogen. The mixture was transferred to a separating funnel and washed with 5% citric acid (50ml), saturated NaHCO3 (50ml), and brine (50ml). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. Ad-PEG500 was purified by column chromatography over silica gel (DCM/MeOH: 9/1) to yield the product E as a yellow oil (1.1g, 83%). Ad-PEG5000 was dissolved in a minimum amount of DCM and precipitated from diethyl ether to yield the product F as a white solid (805mg, 78%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With pyridine; at 0 - 20℃; for 3h; | [Example 1] Preparation of Adamantan-1-carboxylic acid-(3-methyl-4-nitrophenyl)-amide First, 3-methyl-4-nitroaniline (100 mg, 0.65 mmol, 1.1 eq) is dissolved into pyridine (1 ml). Next, adamantane carboxyl chloride (118 mg, 0.59 mmol, 1.0 eq) is added gradually dropwise thereto at 0C. The reaction mixture is agitated at room temperature for 3 hours. The reaction mixture is introduced to and diluted with ethyl acetate. Then, the reaction mixture is washed with 1N aqueous hydrochloric acid twice. After that, the reaction mixture is washed with saline, dried over dry manganese (100 mg), filtered, concentrated and separated by column chromatography to obtain 164 mg of the target product (yield 84%). The NMR results of the product are shown below. It can be seen from the NMR results that the product is adamantan-1-carboxylic acid-(3-methyl-4-nitrophenyl)-amide. 1H NMR (300MHz, CDCl3, delta): 8.03(d, 1 H, J = 9.0 Hz), 7.62(s, 1 H), 7.51-7.48(m, 2H), 2.62(s, 3H), 2.11 (s, 3H), 1.96-1.81(m, 6H), 1.81-1.71(m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15.0 parts of the compound represented by the formula (I-1-a)22.4 parts of N-methylpiperidine,2.2 parts of dimethylaminopyridine and 45 parts of tetrahydrofuran were charged,Followed by stirring at 23 C. for 30 minutes.21.5 parts of the compound represented by the formula (I-1-b) was charged in the obtained mixture,Followed by stirring at 23 C. for 15 hours.To the resulting mixture,200 parts of ethyl acetate and 100 parts of a saturated aqueous ammonium chloride solution were charged,The mixture was stirred at 23 C. for 30 minutes,The organic layer was recovered by standing and liquid separation.To the recovered organic layer,100 parts of ion-exchanged water was charged,The mixture was stirred at 23 C. for 30 minutes,The organic layer was recovered by standing and liquid separation.This washing operation was repeated three times.The collected organic layer was concentrated.By collecting the concentrated mass on a column (Kanto Chemical Co., Ltd. Silica gel 60N (spherical, neutral) 100-210 mum developing solvent: n-heptane / ethyl acetate = 1/1)21.2 parts of a compound represented by the formula (I-1-c) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In 1,4-dioxane; | General procedure: A solution of the appropriate acyl chloride (adamantane-2-carbonyl chloride or 4-substituted benzoyl chloride, 1.3mmol) in dry dioxane (3mL) was added dropwise to a solution of 7a-m, 15, 16, 17 (1.0mmol) in 10mL of the same solvent, maintained at 70C. After the addition was complete, the mixture was refluxed until the formation of hydrogen chloride stopped (1-18h). The solution was concentrated in vacuo and the residue was dissolved in DCM (30mL), washed with NaHCO3 solution (10mL), dried over anhydrous Na2SO4, and evaporated to dryness. The crude product was purified by recrystallization from MeOH or flash column chromatography on silica gel using the reported eluent system. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In 1,4-dioxane; | General procedure: A solution of the appropriate acyl chloride (adamantane-2-carbonyl chloride or 4-substituted benzoyl chloride, 1.3mmol) in dry dioxane (3mL) was added dropwise to a solution of 7a-m, 15, 16, 17 (1.0mmol) in 10mL of the same solvent, maintained at 70C. After the addition was complete, the mixture was refluxed until the formation of hydrogen chloride stopped (1-18h). The solution was concentrated in vacuo and the residue was dissolved in DCM (30mL), washed with NaHCO3 solution (10mL), dried over anhydrous Na2SO4, and evaporated to dryness. The crude product was purified by recrystallization from MeOH or flash column chromatography on silica gel using the reported eluent system. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; | General procedure: A solution of the appropriate acyl chloride (adamantane-2-carbonyl chloride or 4-substituted benzoyl chloride, 1.3mmol) in dry dioxane (3mL) was added dropwise to a solution of 7a-m, 15, 16, 17 (1.0mmol) in 10mL of the same solvent, maintained at 70C. After the addition was complete, the mixture was refluxed until the formation of hydrogen chloride stopped (1-18h). The solution was concentrated in vacuo and the residue was dissolved in DCM (30mL), washed with NaHCO3 solution (10mL), dried over anhydrous Na2SO4, and evaporated to dryness. The crude product was purified by recrystallization from MeOH or flash column chromatography on silica gel using the reported eluent system. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triethylamine; In dichloromethane; for 18h; | A solution of 1-adamantanecarbonyl chloride (198mg, 1mmol) in dry DCM (1mL) was slowly added to a cooled (0-5C) solution of <strong>[14667-47-1]methyl 2-aminopyridine-3-carboxylate</strong> (14) (152mg, 1mmol) and TEA (210muL, 1.5mmol) in dry DCM (3mL). After stirrring for 18h, the solution was diluted with DCM (5mL), washed with saturated solution of NaHCO3 (5mL) and brine (5mL), then dried over anhydrous sodium sulfate, and evaporated to dryness. The crude residue was purified by recrystallization from MeOH to afford the title compound in 40% yield. Mp 183-184C. 1H NMR (200MHz, CDCl3): delta 10.88 (s, 1H), 8.64 (m, 1H), 8.30-8.27 (m, 1H), 7.04-7.01 (m, 1H), 3.94 (s, 3H), 2.10-2.02 (m, 9H), 1.76-1.74 (m, 6H). MS (ESI): m/z 337 [M+Na]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; for 3.2h;Inert atmosphere; | A 25 mL round bottom flask equipped with a magnetic stir bar, was charged with (S)-(+)-2-amino-1-phenylethanol (0.485 grams, 3.53 mmol), N,N-diisopropylethyl amine (0.714 grams, 5.52 mmol), and CH2Cl2 (5 mL). The reaction flask containing the mixture was placed in an ice bath and allowed to equilibrate for 10 minutes while mixing at 300 r.p.m under nitrogen atmosphere. A separate flask was charged with of 1-adamantanecarbonyl chloride (0.756 grams, 3.81 mmol) and CH2Cl2 (5 mL). The 1-adamantanecarbonyl chloride solution was transferred to a 10 mL, pressure equalizing addition funnel which was connected to the 25 mL reaction flask and this solution was added to the reaction flask over 12 minutes. The reaction was mixed at 300 r.p.m. in the melting ice bath and under nitrogen atmosphere for 3 hr. The reaction mixture was added to a 125 mL separatory funnel following the reaction time period. The reaction mixture was extracted with 3*20 mL aliquots of 1N HCl solution and 1*25 mL aliquot of saturated NaCl solution. The organic phase was recovered and dried over anhydrous Na2SO4, filtered, and concentrated under vacuum at 35-40 C. to give 0.941 grams of the intermediate (3S,5S,7S)-N-((S)-2-hydroxy-2-phenylethyl) adamantane-1-carboxamide which was used in the next synthetic step without further purification. LC/MS (ESI) m/z=300 (MH+). 1H NMR (300 MHz, CD3OD): delta 1.65-2.10 (m, 16H), 3.28-3.51 (m, 2H), 4.76 (dd, 1H), 7.20-7.42 (m, 5H). 13C NMR (75 MHz, CD3OD): delta 28.22, 36.19, 38.71, 40.40, 46.58, 72.19, 125.86, 127.21, 127.88, 142.51, 179.70 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The appropriate aminophenol derivative (1.5 mmol) was dissolvedin acetone (1.5 mL) under N2 (g), cooled to 0 C, charged with K2CO3(622 mg, 4.5 mmol), and stirred for 15 min. After that, the appropriateacyl chloride (1.55 mmol) dissolved in acetone (1 mL) was addeddropwise to the reaction mixture at 0 C. The reaction was monitored byTLC and LC-MS spectrometry. Once reaction completion was confirmed,the mixture was filtered, and the filtrate was concentrated invacuo. The solid was extracted using ethyl acetate (10 mL) and brine(10 mL). The organic layer was collected and dried over anhydrousNa2SO4 and concentrated in vacuo. The product was sulfamoylatedwithout further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The appropriate aminophenol derivative (1.5 mmol) was dissolvedin acetone (1.5 mL) under N2 (g), cooled to 0 C, charged with K2CO3(622 mg, 4.5 mmol), and stirred for 15 min. After that, the appropriateacyl chloride (1.55 mmol) dissolved in acetone (1 mL) was addeddropwise to the reaction mixture at 0 C. The reaction was monitored byTLC and LC-MS spectrometry. Once reaction completion was confirmed,the mixture was filtered, and the filtrate was concentrated invacuo. The solid was extracted using ethyl acetate (10 mL) and brine(10 mL). The organic layer was collected and dried over anhydrousNa2SO4 and concentrated in vacuo. The product was sulfamoylatedwithout further purification |
Tags: 2094-72-6 synthesis path| 2094-72-6 SDS| 2094-72-6 COA| 2094-72-6 purity| 2094-72-6 application| 2094-72-6 NMR| 2094-72-6 COA| 2094-72-6 structure
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P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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